Furocoumarins are skin photosensitizers and they are also carcinogenic in certain animal skins. Our goal in the proposed study is two-fold: (1) Elucidation of the molecular mechanism of photosensitizing potency of furocoumarins (psoralens), and (2) application of psoralens as molecular structural probes for nucleic acids and proteins. A variety of furocoumaryl compounds will be used for these aims. These will be linked photochemically to lambda DNA and tRNA, as well as to proteins. Attempts will be made to understand the ground state, dark binding, the mechanism of photo induced modification of the nucleic acids and the consequences of it for biological activity. Thus, for example, we plan to examine the photobinding of psoralen to lambda DNA double helix to look for possible specificities of binding, to examine monoaddition versus crosslinking to the double helix and to see what effect such modifications have on the transcription of the DNA.